A substantial number of reports document the superiority of combinations of cytotoxic drugs in the treatment of Hodgkin's Disease and leukemia. Experimental evidence of the increased efficacy of combination (three drugs) chemotherapy in suppressing humoral antibody (tetanus antitoxin) and allograft immunity (mouse skin grafts) as compared with single drug treatment has previously been reported by the applicants. In the present proposal dog and rabbit recipients of renal allografts will be bilaterally nephrectomized and treated daily with two dose levels of one, two or three drugs (azathioprine, prednisone and cyclophosphamide). The effect of pulsed large doses of intravenously administered methylprednisolone will be ascertained. Long term adaptation to grafts will be evaluated by assessing host macrophage and lymphocyte response to donor antigen in vitro.